Cell surface factors are involved in formation of progressively growing tumors as evidenced by altered expression of normal and coincident appearance of new cell surface properties with tumorigenicity. Plasminogen activator, a protease, is studied in relation to the cell's tumorigenicity and to other frequently altered properties. Guinea pig carcinogenesis in vitro is used to establish the relationship of individual and combined factors to the preneoplastic sequential stages which may precede neoplastic transformation, the acquisition of tumorigenicity, by two years. In this way, the stages and factors associated with carcinogenesis are studied separate from those properties found only in tumorigenic cells. All tumorigenic cells produce plasminogen activator with the amount produced correlating with the (1) tumorigenic threshold inoculum, (2) capacity for anchorage independent growth, (3) ability to induce a tuberculin-like reaction in non-immune guinea pigs, (4) susceptibility to guinea pig lymphotoxin, and (5) reduced expression of cell surface glycolipid (Forssman antigen). Factors whose expression do not correlate with either plasminogen activator production or tumorigenicity include fibronectin production and individually distinct tumor associated cell surface neoantigen expression.